title: Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit.
abstract: We report the cDNA cloning, chromosomal localization, and a mutation in the human nuclear gene encoding the 18-kD (AQDQ) subunit of the mitochondrial respiratory chain complex I. The cDNA has an open reading frame of 175 amino acids and codes for a protein with a molecular mass of 23.2 kD. Its gene was mapped to chromosome 5. A homozygous 5-bp duplication, destroying a consensus phosphorylation site, in the 18-kD cDNA was found in a complex I-deficient patient. The patient showed normal muscle morphology and a remarkably nonspecific fatal progressive phenotype without increased lactate concentrations in body fluids. The child's parents were heterozygous for the mutation. In 19 other complex I-deficient patients, no mutations were found in the 18-kD gene.
authors.affiliation: Department of Pediatrics, University Hospital, Nijmegen, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: van den Heuvel
authors.forename: W
authors.initials: W
authors.lastname: Ruitenbeek
authors.forename: R
authors.initials: R
authors.lastname: Smeets
authors.forename: Z
authors.initials: Z
authors.lastname: Gelman-Kohan
authors.forename: O
authors.initials: O
authors.lastname: Elpeleg
authors.forename: J
authors.initials: J
authors.lastname: Loeffen
authors.forename: F
authors.initials: F
authors.lastname: Trijbels
authors.forename: E
authors.initials: E
authors.lastname: Mariman
authors.forename: D
authors.initials: D
authors.lastname: de Bruijn
authors.forename: J
authors.initials: J
authors.lastname: Smeitink
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D017809:Fatal Outcome; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D007773:Lactates / Q000032:analysis; D008297:Male; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000473:pathology; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D009679:Nuclear Family; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D007773:Lactates; D016660:NAD(P)H Dehydrogenase (Quinone)